SCD Patients Benefit from Early Rivipansel Treatment for VOCs, New Analyses Show

SCD Patients Benefit from Early Rivipansel Treatment for VOCs, New Analyses Show
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Starting treatment with rivipansel (GMI-1070) shortly after vaso-occlusive crisis (VOC) onset significantly shortened hospital stays and the time to opioid discontinuation in children and adults with sickle cell disease (SCD), new analyses of the RESET clinical trial show.

The data further support “the potential benefits of treatment with rivipansel early in the course of VOC, as observed in sickle cell patients in the RESET trial — both in the total patient population as well as in the pediatric subgroup,” Helen Thackray, MD, said in a press release. Thackray is chief medical officer of GlycoMimetics, the therapy’s developer.

“We are engaging in discussions with the FDA [U.S. Food and Drug Administration] to determine what, if any, next steps could be taken to carry this program forward in acute VOC, either in pediatrics or in the overall population,” she said. “This treatment setting remains an area of unmet medical need, as there are no [therapies] approved nor currently in late-stage development for acute intervention,” Thackray said.

These RESET findings, along with positive preclinical data of GMI-1687, another GlycoMimetics’ potential therapy for VOCs, were presented recently at the 15th Annual Scientific Conference on Sickle Cell and Thalassemia (ASCAT) Meeting, held virtually Oct. 26–31. ASCAT also hosted the 1st European Hematology Association Sickle Cell Conference.

Given directly into the bloodstream, rivipansel works by blocking the activity of all three types of selectins (E-, P- and L-selectin), cell adhesion proteins found at high levels in the blood vessels of SCD patients, and that contribute to VOCs.

Since selectins increase blood cells’ stickiness to surfaces and other cells, eventually obstructing blood flow and causing VOCs, rivipansel has the potential to prevent and resolve this serious and common SCD complication.

After a transfer back from Pfizer — its former collaborator in rivipansel’s development — early this year, GlycoMimetics is again the sole owner of the therapy’s commercial and developmental rights and licenses.

Rivipansel received the FDA’s rare pediatric disease designation for SCD, acknowledging its potential to provide clinically meaningful benefits to patients, especially those younger than age 18, with this serious condition.

The RESET Phase 3 trial (NCT02187003) evaluated rivipansel’s safety and effectiveness against a placebo in 345 SCD patients, ages 6 and older, who experienced a VOC requiring hospitalization and intravenous (into-the-vein) opioid treatment for pain management.

The study’s main goal was to assess whether rivipansel was superior to placebo at shortening the time to readiness-for-discharge, defined as the time from the first rivipansel dose to the patient’s readiness to be released from the hospital. This goal reflected the achievement of multiple criteria measuring healthcare utilization and clinical improvement prior to leaving the hospital.

Secondary goals included changes in time to discharge, opioid cumulative use, time to opioid discontinuation, and safety measures.

After RESET’s top-line data showed the trial failed to meet both its main and secondary goals in 2019, a post hoc analysis of the trial’s data — a statistical analysis specified after the data were seen — conducted by GlycoMimetics suggested that SCD patients treated soon after the onset of VOC pain benefited from the therapy.

The analysis showed that participants starting rivipansel treatment up to 26.4 hours after the onset of VOC pain had a significantly shorter median time to readiness-for-discharge (65.7 hours) than those given a placebo (122 hours).

Now, findings from additional post hoc analyses were presented in a poster, titled, “Early Initiation of Treatment with Rivipansel for Acute Vaso-Occlusive Crisis in Sickle Cell Disease (SCD) Achieves Earlier Discontinuation of IV Opioids and Shorter Hospital Stay: RESET Clinical Trial Analysis.

Results showed that early treatment (within the 26.4 hour period after pain onset) also significantly shortened patients’ median time to hospital discharge (by 41.5 hours) and to opioid discontinuation (by 50.5 hours), compared with a placebo.

Notably, similar but less-pronounced benefits also were observed among RESET’s pediatric population — 204 children and adolescents with ages between 6 and 17 years — which accounted for 41% of all participants.

Specifically, pediatric patients treated with rivipansel within 30 hours of VOC onset took significantly less time to be ready for discharge-ready (29.3 hours less), discharged (23.2 hours), and opioid use-free (15.4 hours). More of these children also were ready for discharge after one, two, and three days, compared with those given a placebo.

In addition, patients receiving rivipansel had a 59% drop in E-selectin levels, while those on a placebo showed a 9% increase, highlighting that the therapy had the intended biological effect.

Rivipansel’s safety profile was comparable with that of the placebo.

“In addition to highlighting the importance of treating individuals early in the course of their acute painful crisis, these new findings confirm the critical role of E-selectin in acute vaso-occlusion and the opportunity to resolve that occlusion and pain with effective intervention,” Thackray said.

In an oral presentation titled “Treatment of Acute Vaso-occlusion in Mouse Models of Sickle Cell Disease Following Intravenous or Subcutaneous Administration of a Highly Potent E-selectin Specific Inhibitor,” GlycoMimetics presented preclinical data of its second candidate therapy for VOCs, GMI-1687.

GMI-1687, given through under-the-skin injections (with the potential to be self-administered by patients), is a more selective and highly potent E-selectin suppressor. Using two mouse models of SCD, researchers showed that GMI-1687 prevented sickle red blood cells from sticking to blood vessels and obstructing blood flow, supporting its therapeutic potential for managing and preventing VOCs in SCD patients.

Marta Figueiredo holds a master’s in evolutionary and developmental biology and a PhD in biomedical sciences from the University of Lisbon, Portugal. Her research is focused on the role of several signaling pathways in thymus and parathyroid glands embryonic development.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marta Figueiredo holds a master’s in evolutionary and developmental biology and a PhD in biomedical sciences from the University of Lisbon, Portugal. Her research is focused on the role of several signaling pathways in thymus and parathyroid glands embryonic development.
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